Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease that occurs as a major complication of premature infants due to prolonged mechanical ventilation, the main features of bronchopulmonary dysplasia are increased inflammation, the inhibition of angiogenesis, damaged alveoli, and the like, and bronchopulmonary dysplasia causes the high mortality rate of premature babies, but despite long studies on bronchopulmonary dysplasia, it is impossible to treat bronchopulmonary dysplasia.
Formyl-peptide receptor type 2 (FPR2), which is a G-protein coupled receptor, is known to be expressed in various types of cells. The earliest discovered functions of FPR2 include inflammation control in immune cells such as white blood cells and various contributions to cellular metabolism. FPR2 is known to not only perform anti-inflammatory functions, but also mediate cell proliferation, migration, and angiogenesis in endothelial cells. FPR2 activation is known to increase cytoplasmic calcium levels that induce cell signaling, such as the ERK pathway, and to increase chemotaxis, cell proliferation, and angiogenesis in order to maintain tissue homeostasis in damaged tissues in a manner dependent on specific cell types and microenvironment.
Meanwhile, WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met, a synthetic peptide) (SEQ ID NO: 1), which is a synthetic peptide identified by screening peptide libraries, is known as a potent agonist of FPR2 that activates leukocytes. In previous studies, it was confirmed that WKYMVm (SEQ ID NO: 1) increased cell survival and migration through FPR2, and increased angiogenesis in endothelial cells in vitro. In addition, in in vivo studies, it was confirmed that WKYMVm (SEQ ID NO: 1) promoted angiogenesis and tissue repair.
Previous studies have shown that lipoxin A4 and resolvin D1, which bind to FPR2, improve alveolar damage caused by bronchopulmonary dysplasia in neonatal mice (Martin C R, Zaman M M, Gilkey C, Salguero M V, Hasturk H, et al. (2014) PLoS One 9: e98773.), but an effect of WKYMVm (SEQ ID NO: 1) on lung damage due to bronchopulmonary dysplasia has not been known. In addition, the use of WKYMVm (SEQ ID NO: 1) in the treatment of hyperoxia-induced lung injury has not yet been adequately studied.